Treatment > STI571

Meeting Abstract

CD 117 (c-kit) - predictive for efficacy of imatinib in pretreated glioblastoma patients?

Gregor Dresemann

Franz-Hospital Dülmen, Onkologische Abteilung, Dülmen, Germany

Epidermal growth factor receptors (EGFR) were detected in malignancies of the brain including glioblastoma (GB).
Imatinib (GLEEVEC (R)) is a signal transduction inhibitor for EGFR with remarkable efficacy in chronic myeloic leukemia and gastrointestinal stroma tumour (GIST).
It seems obvious that efficacy of imatinib in GIST depends on the presence of CD 117 a subtype of EGFR.
GB patients with tumour progression after irradiation therapy and chemotherapy containing ACNU and temozolomide have a rather poor prognosis.
Magnetic resonance imaging (MRI) should be performed in GB patients every 6 weeks to detect progression before dramatic decrease in ECOG performance status (PS), the main prognostic factor.
We analysed the efficacy of imatinib in a group of 6 progressive GB patients pretreated with irradiation and with ACNU and temozolomide containing chemotherapy schedules, PS was 2.
CD 117 was analysed subsequently.
All patients were treated with imatinib 400 mg total oral dose/day continuously combined with hydroxycarbamid 1000 mg total oral dose/day continuously in 4 cases, in 2 cases combined with CAELYX (R) ( = doxorubicin encysted with liposoms) 30 mg/m2 infusion every 28 days.
Combination was chosen to assist imatinib entering metabolism of the brain, while imatinib might block tumour proliferation which also is one reason for development of chemotherapy resistance.
The median treatment period was 9.6 weeks (8 to 18) with stable disease (SD) in 2 cases, minor response (MR) in 2 cases and partial response (PR) in 2 cases, there were no tumour or treatment related deaths and no measurable progression in this period, 1 patient with MR died of pulmonary embolism, 1 patient with PR could improve PS to 1, in 4 patients PS remained unchanged. 2 patients were histological CD 117 positive (1 SD, 1MR) 4 patients were negative (1 SD, 1 MR, 2 PR).
In the reported group of patients combination therapy of imatinib with low toxicity chemotherapy was well tolerated and effective independent from CD 117 although present observation time is short.
We try to confirm these data in a phase I/II trial in order to transfer this strategy to earlier stage GB.
Other subtypes of EGRF should be examined.

© Copyright 2002 American Society of Clinical Oncology